Jungnam Joo

Site-Specific Risk Factors for Colorectal Cancer in a Korean Population

We investigated the association of colorectal cancer risk factors with different colorectal cancer subsites to assess etiological differences for cancers of the proximal colon, distal colon, and rectum. Included in this study were 869,725 men and 395,501 women who participated in a health examination provided by the Korean National Health System between 1996 and 1997. During up to 7 years of follow-up, 4,144 incident colorectal cancer cases were detected (3,051 men and 1,093 women). Greater height was associated with elevated risk for distal colon cancer and rectal cancer in both men and women. Family history of cancer was associated with higher risk for cancers of the proximal colon in men and distal colon in both men and women. Frequent alcohol consumption and consuming high amounts of alcohol were associated with elevated risk for distal colon cancer in men and higher risk for rectal cancer in women. Frequent meat consumption was associated with risk for proximal colon cancer in men and for rectal cancer in women. Our findings suggest that risk factors for colorectal cancer are different by subsites of colon and rectum, as well as by sex.

Treatment of spontaneous arterial dissections with stent placement for preservation of the parent artery.

SummaryBackground. A wide variety of treatment regimens have been advocated for dissections involving the intracranial arteries. Recently, the stent can be used to exclude the aneurysm from the circulation and preserve the parent artery. We evaluated the safety and efficacy of stent angioplasty for intracranial arterial dissections.Methods. Ten patients with spontaneous dissections, nine vertebral artery and one internal carotid artery lesions underwent endovascular treatment using stent placement as primary treatment modality. One stent placement was attempted in five patients initially. Three patients were intentionally treated with two overlapping stents which completely covered the aneurysm orifice. Two tandem stents were used in one patient to allow spanning the entire length of the dissection. Stent-assisted coil embolization was performed in one patient.Results. Of the 10 patients in whom stenting was tried, the overall success in reaching the target lesion with stents was 90%. Of the 9 patients treated with stents, stent release and positioning were considered optimal in 7 patients (77.8%) and suboptimal in two. Lesions of 8 patients were improved or stable in angiographic follow-up. However, one pseudo-aneurysm was enlarged, and subsequently, was treated by proximal occlusion using coils. There were no instances of postprocedural ischaemic attacks, new neurological deficits, and no new minor or major strokes prior to patient discharge. All parent arteries of the patient who underwent the successful procedure were preserved. On the modified Rankin scale used for the follow up, all patients were assessed as functionally improved or of stable clinical status.Conclusions. The success in reducing dissection-induced stenosis or pseudo-aneurysm, the patency rate obtained at follow-up, and the lack of strokes (ischaemic or haemorrhagic) suggest that stent placement offers a viable alternative to complex surgical procedures or deconstructive procedures. The long-term efficacy and durability of stent placement for arterial dissection remains to be determined in a large series.

Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study

The prognostic significance of inherited genetic variants in advanced-stage non-small cell lung cancer (NSCLC) patients remains unknown. In this study, we genotyped 271 817 single-nucleotide polymorphisms in 348 advanced NSCLC patients who received chemotherapy and analyzed their association with prognosis by using Cox proportional hazard regression model adjusted for known prognostic factors. Top candidate single-nucleotide polymorphisms (SNPs) were selected using the bootstrap re-sampling procedure. Median age of patient population was 56 years. Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and 80.4%, respectively. We identified 17 top candidate SNPs related to prognosis using cut-off minimum P value of <5.0 × 10(-5) in at least 70% of 1000 bootstrap samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A, DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall survival in dominant model [AG+GG to AA, hazard ratio (HR) of death (95% CI) = 0.53 (0.42-0.67); P = 2.025 × 10(-7)]. The SNP at 4q25:EGF, rs11098063, for which some genetic variations was previously reported to be associated with prognosis, also showed significant association with overall survival in additive model [CC versus CT versus TT, HR (95% CI) = 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19-0.79); P = 9.582 × 10(-6)]. Survival differences according to the genotype of these SNPs were independent of sex, smoking, histology and chemotherapy regimens. These results suggested the variants at multiple genetic loci might contribute to the risk of death in advanced NSCLC patients receiving chemotherapy.

Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer.

Introduction: Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non–small-cell lung cancer. Methods: Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients’ survival and symptom responses, including intracranial pressure (ICP) control. Results: There were 44 men and 61 women, with a median age of 56 years (range, 31–75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1–49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5–21.5 months). Age (≥60 years), poor Karnofsky performance score (< 70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis. Conclusion: Intraventricular chemotherapy for patients with LMC from non–small-cell lung cancer could palliate associated symptoms and prolong patients’ survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.

Risk of Pancreatic Cancer in Relation to ABO Blood Group and Hepatitis C Virus Infection in Korea: A Case-Control Study

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.

Worse outcome of sorafenib therapy associated with ascites and Child-Pugh score in advanced hepatocellular carcinoma

The outcomes of sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC) and impaired liver function remain unresolved. Although Child–Pugh (CP) classification is widely used for patient categorization, heterogeneity within a given CP class makes outcomes less predictable. The aim was to investigate the prognostic significance of CP score elements on the outcome of sorafenib in patients with advanced HCC and impaired liver function.

Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma

Background and Aim:  Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization (TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE.

Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association With Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer.

BACKGROUND The immune system might influence breast cancer (BC) prognosis. However, the relationship between programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocyte (TIL) profiles remains unclear with respect to BC subtypes. PATIENTS AND METHODS We investigated the relationship between TIL profiles for CD8+ and forkhead box P3-positive (FOXP3+) and PD-L1 expression in primary tumor tissue using immunohistochemistry and the clinical outcomes in 2 patient cohorts at the National Cancer Center: 256 patients diagnosed with early-stage BC from January 2001 to December 2005 and 77 hormone receptor (HR)-negative BC patients diagnosed from January 2006 to December 2008. Clinical data were collected, including HR status, human epidermal growth factor receptor 2 expression, disease-free survival, and overall survival (OS). RESULTS The median patient age was 47 years (range, 28-78), and the median follow-up period was 9.8 years. Of the 333 patients, 186 (55.9%) had HR-positive and 125 (37.5%) had node-positive BC. We found a strong positive correlation between CD8+ TILs and FOXP3+ TILs (P < .001). CD8+ TILs were more abundant in tumors with low PD-L1 expression (P < .001), although no association was found between FOXP3+ TILs and PD-L1 expression. More CD8+ TILs were present in HR-negative than in HR-positive BC (P < .001), and PD-L1 expression was more frequent in HR-positive BC (P < .001). A greater number of CD8+ TILs (increase in quartile) was strongly associated with OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.95; P = .03) only in HR-negative BC when adjusted for various clinical factors. PD-L1 expression and FOXP3+ TILs did not exhibit such associations. CONCLUSION Higher CD8+ lymphocyte infiltration was related to lower PD-L1 expression and higher FOXP3+ TIL infiltration in BC. Higher CD8+ TIL expression was associated with prolonged survival only in those with HR-negative BC.

Learning curve analysis of laparoscopic radical hysterectomy and lymph node dissection in early cervical cancer.

OBJECTIVE We aimed to evaluate the learning curve for laparoscopic radical hysterectomy and lymph node dissection (LRHND) in uterine cervical cancer and to compare the surgicopathologic outcomes of cases treated in the first half of the curve with those treated in the second half of the curve. STUDY DESIGN The medical records of LRHND patients between August 2004 and April 2011 were reviewed retrospectively. The patients were divided into two groups of the first 35 cases (phase I) and the second 35 cases (phase II). All operations were performed by the same surgeon. Demographic data and surgicopathologic parameters were analyzed. The learning curve was evaluated using the cumulative summation (CUSUM) technique. RESULTS No difference was found in demographics and histologic type between the two groups. The mean operating time (307.7±85.8 min) of phase I was significantly longer than phase II (266.3±58.8 min) (P=0.021). The number of complications in phase I patients (N=9) was significantly higher than that (N=1) of phase II patients (P=0.013). There were no significant differences between the two groups with respect to lymph node yield and likelihood of identifying positive lymph nodes, resection margins, parametrium, stromal invasion, and lymphovascular space invasion. Disease-free survival did not differ between the two groups (P=0.142). The learning period for LRHND to reach a turning point was calculated to be 40 cases. CONCLUSIONS An extended learning period can be required for LRHND, during which survival and pathologic outcome of LRHND may not be adversely affected.

Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy.

Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. However, there has been little work on how HPV integration status relates to treatment outcome for cervical carcinomas. In the current study, HPV E2 and E6 gene copy numbers were measured in 111 cervical cancer tissues using real-time QPCR. Integration patterns were divided into four groups: single copy-integrated with episomal components (group 1), single copy-integrated without episomal components (group 2), multicopy tandem repetition-integrated (group 3), and low HPV (group 4) groups. A relapse-predicting model was constructed using multivariable Cox proportional hazards model to classify patients into different risk groups for disease-free survival (DFS). The model was internally validated using bootstrap resampling. Oligonucleotide microarray analysis was performed to evaluate gene expression patterns in relation to the different integration groups. DFS rate was inferior in the order of the patients in group 4, group 2/3, and group 1. Multivariate analysis showed that histologic grade, clinical stage group, and integration pattern were significant prognostic factors for poor DFS. The current prognostic model accurately predicted the risk of relapse, with an area under the receiver operating characteristic curve (AUC) of 0.74 (bootstrap corrected, 0.71). In conclusion, these data suggest that HPV integration pattern is a potent prognostic factor for tailored treatment of cervical cancer.